238-OR: Effect of Baseline Antihyperglycemic Medications on Weight Reduction with Tirzepatide—SURMOUNT-2 Subgroup Analysis

Background: Antihyperglycemic medication (AHM) may influence body weight causing weight gain or weight reduction. In SURMOUNT-2, tirzepatide, a once weekly GIP/GLP-1 receptor agonist, resulted in significantly greater weight reduction compared to placebo in participants with BMI ≥27 kg/m2 and type 2 diabetes. We conducted a subgroup analysis to explore the association between the weight-reduction efficacy of tirzepatide and concomitant AHMs at randomization categorized as promoting weight loss (WL), weight gain (WG), or weight neutral (WN). Methods: A mixed model for repeated measures assessed the change in body weight from randomization to endpoint (week 72). Logistic regression was conducted to analyze the proportion of participants achieving ≥5%, ≥10%, and ≥15% weight reduction targets at endpoint. Results: At baseline, mean weight was 95.7, 100.6, and 101.8 kg and BMI was 34.5, 36.0, and 36.4 kg/m2 in the WL, WG, and WN subgroups, respectively. Tirzepatide resulted in significantly greater weight reduction than placebo in all AHM subgroups (all p0.001). No differences were observed among tirzepatide-treated AHM subgroups in the percent change in body weight and the proportion of participants achieving weight reduction targets. Conclusion: Tirzepatide was superior to placebo for weight reduction and showed similar weight reduction efficacy across AHM subgroups. Disclosure S. Machineni: Research Support; Eli Lilly and Company. Advisory Panel; Eli Lilly and Company. Consultant; Novo Nordisk. Research Support; Rhythm Pharmaceuticals, Inc. Consultant; Rhythm Pharmaceuticals, Inc. F. Jaouimaa: Employee; Eli Lilly and Company. R. Griffin: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. M.X. Zhang: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. J. Fraseur Brumm: None. Funding Eli Lilly and Company